A. Field of the Invention
The invention is concerned with the analysis of samples withdrawn from a sample cup by a probe and thereafter injected into a measuring cell containing a suitable reagent with some reaction between the sample and the reagent being measured to accomplish the analysis. The invention has its application particularly to medical procedures where samples of body fluids, blood plasma or serum and the like can be analyzed promptly after the sample is withdrawm from the patient. In such procedures the analysis is determined by obtaining the glucose value or the BUN (Blood-Urea-Nitrogen) value when the sample is ejected into an enzyme reagent and the maximum rate of reaction is measured. In one procedure glucose is determined by means of oxygen rate method employing an oxygen sensor, in another procedure conductivity rate method is employed. Owing to the fact that the analysis is determined by the maximum rate of the reaction which is permitted to go on for a period of time, and this rate is critically determined by the quantity of sample reacting, it is very important that precisely metered samples be introduced into the measuring and reacting cells and that no extraneous material be permitted to enter the cell.
B. Description of the Prior Art
A glucose analyzer is described in an operating manual published by Beckman Instruments, Inc. of Fullerton, California, identified as Beckman Instructions 015-083513-F November, 1973, 731198 015-083513, copyright 1969. This manual describes how a precise volume of sample is manually pipetted into enzyme reagent in a cell containing a sensor that responds to oxygen concentration. Solid state electronic circuitry determines the rate of oxygen consumption, which is directly proportional to the concentration of glucose in the sample. In the description of pipetting methods it is pointed out that operator performance during sample introduction determines the quality of results that the instrument will furnish and that close attention to the details of the sampling procedure is required if the precision of the instrument is not to be compromised. It is also explained that, for pipettes of the type having a significant "dead volume" remaining air volume within the enclosed sealed portion of the sampling system, the amount of sample picked up is dependent upon the depth to which the tip is immersed into the liquid. In this type of pipette a volume of air is displaced and the sample picked up by the movement of a sealed piston. The operating manual also explains that the liquid level effect does not occur when a special type of pipette is employed with three positions of the actuator instead of only two.
Nevertheless there is also the necessity for avoiding retention of a residue of sample on the outside of the pipette tip, since the sample material retained on the outside of the pipette tip can represent a significant fraction of 10 .mu.l, which is the order of magnitude of the samples. Wiping off the tip with tissue must be avoided because there is a risk of incomplete wipe-off or of withdrawing liquid from the pipette by capillary action and also the possibility of infection of the operator in the case of certain fluids being analyzed. A less operator-sensitive technique is therefore recommended which consists of dipping the tip into a distilled water rinse. As the tip is slowly withdrawn from the rinse water, surface forces strip liquid from the outside of the tip and eliminate the need for wiping with a tissue.
The said operating manual also describes a measurement cell with separate, manually operated syringe-type plunger pumps for filling the measurement cell from a reagent reservoir and for draining the measurement cell after an analysis has been made by means of the oxygen sensor.
Liquid analysis apparatus having an oxygen sensor, a magnetically coupled stirrer in a measurement cell, two thumb operated barrel pumpts with spring return, one for filling the measurement cell with reagent and the other for draining reagent from the measurement cell is described in U.S. Pat. No. 3,701,716 issued to Deuringer, Ray and Sternberg.
Apparatus for dipping a pair of sample probes into a sample cup, and transferring them to horizontally separated positions for ejection of the samples into two measurement cells is described in U.S. Pat. No. 3,853,008 of Jack L. Hoffa assigned to the same assignee as the present application. Another form of apparatus for automatically aspirating sample from sample cups and transferring samples to reagent cells is described in U.S. Pat. No. 3,617,222 to Matte. The latter patent also describes mechanism for bringing successive sample cups or test tubes into position.
U.S. Pat. No. 3,266,322 Negersmith et al. describes liquid sample supply and wash apparatus for an automatic analysis system with different sample cups on a rotating plate. A rotating plate cup carrier is described also in U.S. Pat. No. 2,879,141 to Skeggs.
It is an object of the invention to provide an improved procedure for clinical sample analysis in which a sample is not merely picked up and introduced into a reaction cell with great precision but also without contaminating carryover into the next sample. A further object of the invention is to provide fully automatic or semi-automatic apparatus for sample analysis, especially for glucose analysis and for blood urea nitrogen analysis in which sample contamination is avoided.
It is still another object of the invention to provide an improved system for cleaning probe tips and removing external sample residue coating.
Other and further objects, features and advantages of the invention will become apparent as the description proceeds.